ES2790859T3 - Tratamiento para hipertensión pulmonar - Google Patents
Tratamiento para hipertensión pulmonar Download PDFInfo
- Publication number
- ES2790859T3 ES2790859T3 ES16182514T ES16182514T ES2790859T3 ES 2790859 T3 ES2790859 T3 ES 2790859T3 ES 16182514 T ES16182514 T ES 16182514T ES 16182514 T ES16182514 T ES 16182514T ES 2790859 T3 ES2790859 T3 ES 2790859T3
- Authority
- ES
- Spain
- Prior art keywords
- therapeutic agent
- oral
- inhaled
- treprostinil
- pulmonary hypertension
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000002815 pulmonary hypertension Diseases 0.000 title claims abstract description 27
- 238000011282 treatment Methods 0.000 title claims description 18
- PAJMKGZZBBTTOY-ZFORQUDYSA-N treprostinil Chemical group C1=CC=C(OCC(O)=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 PAJMKGZZBBTTOY-ZFORQUDYSA-N 0.000 claims abstract description 65
- 239000003814 drug Substances 0.000 claims abstract description 55
- 229960005032 treprostinil Drugs 0.000 claims abstract description 46
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 45
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 229960002890 beraprost Drugs 0.000 claims abstract description 13
- CTPOHARTNNSRSR-APJZLKAGSA-N beraprost Chemical group O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)C(C)CC#CC)C1=C2C=CC=C1CCCC(O)=O CTPOHARTNNSRSR-APJZLKAGSA-N 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 238000001990 intravenous administration Methods 0.000 claims description 21
- 238000001802 infusion Methods 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 17
- 238000002560 therapeutic procedure Methods 0.000 claims description 17
- 208000002193 Pain Diseases 0.000 claims description 5
- 230000009885 systemic effect Effects 0.000 claims description 5
- 208000001953 Hypotension Diseases 0.000 claims description 4
- 206010033425 Pain in extremity Diseases 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 230000036543 hypotension Effects 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 238000011260 co-administration Methods 0.000 claims description 3
- 230000000977 initiatory effect Effects 0.000 claims description 2
- 159000000000 sodium salts Chemical group 0.000 claims 2
- 230000001934 delay Effects 0.000 claims 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 38
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 30
- 229960001123 epoprostenol Drugs 0.000 description 28
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 21
- 229940014025 tyvaso Drugs 0.000 description 19
- 238000002648 combination therapy Methods 0.000 description 15
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical group COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 13
- 229960003065 bosentan Drugs 0.000 description 13
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 12
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 12
- 230000008901 benefit Effects 0.000 description 11
- 229960003310 sildenafil Drugs 0.000 description 11
- IQKAWAUTOKVMLE-ZSESPEEFSA-M treprostinil sodium Chemical group [Na+].C1=CC=C(OCC([O-])=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 IQKAWAUTOKVMLE-ZSESPEEFSA-M 0.000 description 11
- 229940079593 drug Drugs 0.000 description 9
- 229940118867 remodulin Drugs 0.000 description 9
- 229960002240 iloprost Drugs 0.000 description 7
- 238000013459 approach Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 210000001147 pulmonary artery Anatomy 0.000 description 6
- 230000002685 pulmonary effect Effects 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 150000003815 prostacyclins Chemical class 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000002459 sustained effect Effects 0.000 description 5
- 229940105295 ventavis Drugs 0.000 description 5
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940124447 delivery agent Drugs 0.000 description 4
- 210000003038 endothelium Anatomy 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 229940127293 prostanoid Drugs 0.000 description 4
- 150000003814 prostanoids Chemical class 0.000 description 4
- 229960000835 tadalafil Drugs 0.000 description 4
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 4
- 210000005166 vasculature Anatomy 0.000 description 4
- RHWRWEUCEXUUAV-ZSESPEEFSA-N 2-[[(1r,2r,3as,9as)-2-hydroxy-1-[(3s)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1h-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid;2-(2-hydroxyethylamino)ethanol Chemical compound OCCNCCO.C1=CC=C(OCC(O)=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 RHWRWEUCEXUUAV-ZSESPEEFSA-N 0.000 description 3
- 102000002045 Endothelin Human genes 0.000 description 3
- 108050009340 Endothelin Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000000702 anti-platelet effect Effects 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000003305 oral gavage Methods 0.000 description 3
- 230000006995 pathophysiological pathway Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 230000024883 vasodilation Effects 0.000 description 3
- 229940124549 vasodilator Drugs 0.000 description 3
- 239000003071 vasodilator agent Substances 0.000 description 3
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 2
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002308 endothelin receptor antagonist Substances 0.000 description 2
- 210000003989 endothelium vascular Anatomy 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 231100000824 inhalation exposure Toxicity 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 230000001839 systemic circulation Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000003767 thromboxane receptor stimulating agent Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- 102000010180 Endothelin receptor Human genes 0.000 description 1
- 108050001739 Endothelin receptor Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000009079 Epoprostenol Receptors Human genes 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108091006335 Prostaglandin I receptors Proteins 0.000 description 1
- 206010039163 Right ventricular failure Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229950000586 aviptadil Drugs 0.000 description 1
- 108010006060 aviptadil Proteins 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 208000037815 bloodstream infection Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 229940041682 inhalant solution Drugs 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000004088 pulmonary circulation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000001321 subclavian vein Anatomy 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960001726 treprostinil sodium Drugs 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/558—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
- A61K31/5585—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5578—Eicosanoids, e.g. leukotrienes or prostaglandins having a pentalene ring system, e.g. carbacyclin, iloprost
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28265910P | 2010-03-15 | 2010-03-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2790859T3 true ES2790859T3 (es) | 2020-10-29 |
Family
ID=43858371
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16182514T Active ES2790859T3 (es) | 2010-03-15 | 2011-03-14 | Tratamiento para hipertensión pulmonar |
| ES11711190.6T Active ES2611187T3 (es) | 2010-03-15 | 2011-03-14 | Tratamiento para hipertensión pulmonar |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11711190.6T Active ES2611187T3 (es) | 2010-03-15 | 2011-03-14 | Tratamiento para hipertensión pulmonar |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8609728B2 (enExample) |
| EP (2) | EP3108888B1 (enExample) |
| JP (4) | JP5681276B2 (enExample) |
| KR (3) | KR20160132501A (enExample) |
| CN (1) | CN102883722B (enExample) |
| CA (2) | CA2791081C (enExample) |
| ES (2) | ES2790859T3 (enExample) |
| WO (1) | WO2011115922A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101903324B (zh) | 2007-12-17 | 2013-07-03 | 联合治疗公司 | 一种制备Remodulin中的活性成分曲前列素的改良方法 |
| KR20160132501A (ko) | 2010-03-15 | 2016-11-18 | 유나이티드 세러퓨틱스 코오포레이션 | 폐고혈압의 치료 |
| CN103261142B (zh) | 2010-06-03 | 2014-12-10 | 联合治疗公司 | 曲前列环素的制备 |
| US8461393B2 (en) | 2011-03-02 | 2013-06-11 | United Therapeutics Corporation | Synthesis of intermediate for treprostinil production |
| US9387214B2 (en) | 2012-01-13 | 2016-07-12 | United Therapeutics Corporation | Method of identifying therapies for pulmonary hypertension |
| JP2016517410A (ja) | 2013-03-14 | 2016-06-16 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニルの固体形態 |
| US20140275616A1 (en) | 2013-03-15 | 2014-09-18 | United Therapeutics Corporation | Salts of treprostinil |
| KR102238501B1 (ko) | 2013-03-25 | 2021-04-08 | 유나이티드 세러퓨틱스 코오포레이션 | 링커 티올 및 peg화된 형태를 갖는 프로스타시클린 화합물의 제조 방법 |
| EA031604B1 (ru) | 2013-10-25 | 2019-01-31 | Инсмед Инкорпорейтед | Трепростинильные соединения, композиции и способы их использования |
| US20160317542A1 (en) | 2013-12-09 | 2016-11-03 | Respira Therapeutics, Inc. | Pde5 inhibitor powder formulations and methods relating thereto |
| EP3164155B1 (en) | 2014-06-13 | 2022-02-09 | United Therapeutics Corporation | Treprostinil formulations |
| JP6224872B1 (ja) | 2014-10-20 | 2017-11-01 | ユナイテッド セラピューティクス コーポレイション | プロスタサイクリン誘導体を生成するための中間体の合成 |
| EP3221291B1 (en) | 2014-11-18 | 2021-03-31 | Insmed Incorporated | Methods of manufacturing treprostinil and treprostinil derivative prodrugs |
| AU2017296040C1 (en) * | 2016-07-15 | 2023-06-22 | Acceleron Pharma Inc. | Compositions and methods for treating pulmonary hypertension |
| KR102541885B1 (ko) | 2016-09-26 | 2023-06-12 | 유나이티드 쎄러퓨틱스 코포레이션 | 트레프로스티닐 프로드럭 |
| CN110381951A (zh) | 2016-12-14 | 2019-10-25 | 瑞必治公司 | 用于治疗肺性高血压和其他肺病症的方法及组合物 |
| KR20190030805A (ko) * | 2017-09-14 | 2019-03-25 | 경상대학교산학협력단 | 폐고혈압 예방 또는 치료용 흡입제, 및 이의 투여방법 |
| HU231296B1 (hu) * | 2018-03-09 | 2022-09-28 | Chinoin Zrt | Eljárás treprostinil-dietanol-amin só B polimorf formájának előállítására |
| AU2019344541B2 (en) | 2018-09-18 | 2022-01-06 | Eli Lilly And Company | Erbumine salt of treprostinil |
| KR20220002600A (ko) | 2019-04-29 | 2022-01-06 | 인스메드 인코포레이티드 | 트레프로스티닐 전구약물의 건조 분말 조성물 및 이의 사용 방법 |
| KR20210149157A (ko) | 2019-05-14 | 2021-12-08 | 파모사 바이오팜 인코포레이티드 | 약산성 약물의 약제학적 조성물 및 투여 방법 |
| CA3149358A1 (en) | 2019-08-23 | 2021-03-04 | United Therapeutics Corporation | Treprostinil prodrugs |
| CN115916212A (zh) | 2020-04-17 | 2023-04-04 | 联合治疗公司 | 曲前列尼尔用于治疗间质性肺病 |
| WO2021252446A1 (en) | 2020-06-09 | 2021-12-16 | United Therapeutics Corporation | Fumaryl diketopiperidine prodrugs of treprostinil |
| IL303668A (en) | 2020-12-14 | 2023-08-01 | United Therapeutics Corp | Stable treprostinil prodrugs and their uses for the treatment of diseases |
| WO2022187352A1 (en) | 2021-03-03 | 2022-09-09 | United Therapeutics Corporation | A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp) |
| JP2025506019A (ja) | 2022-02-08 | 2025-03-05 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニルイロプロスト併用療法 |
| JP2025515512A (ja) | 2022-04-29 | 2025-05-15 | 兆科薬業（広州）有限公司 | トレプロスチニルソフトミスト吸入剤 |
| IL322116A (en) | 2023-01-19 | 2025-09-01 | United Therapeutics Corp | Analogues of treprostinil |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4306075A (en) | 1980-03-28 | 1981-12-15 | The Upjohn Company | Composition and process |
| GB8814438D0 (en) | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
| GB9011588D0 (en) | 1990-05-24 | 1990-07-11 | Wellcome Found | Prostaglandin analogues for use in medicine |
| GB9311920D0 (en) * | 1993-06-09 | 1993-07-28 | Pfizer Ltd | Therapeutic agents |
| CN1142781C (zh) | 1997-11-14 | 2004-03-24 | 联合治疗公司 | 9－脱氧－2′,9－α－亚甲基－3－氧杂－4,5,6－三去甲－3,7－(1′,3′－间亚苯基)－13,14－二氢－前列腺素F1在治疗外周血管疾病中的用途 |
| US6521212B1 (en) | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
| US6803386B2 (en) | 2002-01-16 | 2004-10-12 | United Therapeutics Corporation | Prostacyclin derivative containing compositions and methods of using the same for the treatment of cancer |
| CA2959852A1 (en) | 2003-05-22 | 2005-01-27 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
| ES2331187T3 (es) | 2003-12-16 | 2009-12-23 | United Therapeutics Corporation | Utilizacion de treprostinil para mejorar las funciones renales. |
| CN101647792B (zh) | 2003-12-16 | 2012-11-28 | 联合治疗公司 | 曲前列环素在制备治疗和预防缺血性损害的药物中的用途 |
| DE602005020269D1 (de) | 2004-04-12 | 2010-05-12 | United Therapeutics Corp | Verwendung von treprostinil zur behandlung von neuropathischen diabetischen fussgeschwüren |
| KR101390579B1 (ko) | 2006-05-15 | 2014-05-19 | 유나이티드 세러퓨틱스 코오포레이션 | 정량 흡입기를 사용한 트레프로스티닐 투여 |
| WO2008049000A2 (en) | 2006-10-18 | 2008-04-24 | United Therapeutics Corporation | Combination therapy for pulmonary arterial hypertension |
| EP2120961A1 (en) | 2007-02-09 | 2009-11-25 | United Therapeutics Corporation | Treprostinil treatment for interstitial lung disease and asthma |
| EP2200650B1 (en) | 2007-09-07 | 2016-01-06 | United Therapeutics Corporation | Buffer solutions having selective bactericidal activity against gram negative bacteria and methods of using same |
| US8350079B2 (en) | 2008-05-08 | 2013-01-08 | United Therapeutics Corporation | Treprostinil formulation |
| JP2012503668A (ja) | 2008-09-25 | 2012-02-09 | アラダイム コーポレーション | 肺深部へのトレプロスチニルの肺送達 |
| KR101544246B1 (ko) | 2009-05-07 | 2015-08-12 | 유나이티드 세러퓨틱스 코오포레이션 | 프로스타시클린 유사체의 고체 제제 |
| KR20160132501A (ko) | 2010-03-15 | 2016-11-18 | 유나이티드 세러퓨틱스 코오포레이션 | 폐고혈압의 치료 |
| US20120010159A1 (en) | 2010-07-09 | 2012-01-12 | United Therapeutics Corporation | Combination therapies with cox-2 inhibitors and treprostinil |
-
2011
- 2011-03-14 KR KR1020167031528A patent/KR20160132501A/ko not_active Ceased
- 2011-03-14 CA CA2791081A patent/CA2791081C/en active Active
- 2011-03-14 US US13/047,033 patent/US8609728B2/en active Active
- 2011-03-14 CA CA2892104A patent/CA2892104C/en active Active
- 2011-03-14 ES ES16182514T patent/ES2790859T3/es active Active
- 2011-03-14 CN CN201180023177.8A patent/CN102883722B/zh active Active
- 2011-03-14 KR KR1020127026242A patent/KR101508047B1/ko active Active
- 2011-03-14 KR KR1020157004406A patent/KR20150027846A/ko not_active Ceased
- 2011-03-14 EP EP16182514.6A patent/EP3108888B1/en active Active
- 2011-03-14 JP JP2013500129A patent/JP5681276B2/ja active Active
- 2011-03-14 WO PCT/US2011/028390 patent/WO2011115922A1/en not_active Ceased
- 2011-03-14 ES ES11711190.6T patent/ES2611187T3/es active Active
- 2011-03-14 EP EP11711190.6A patent/EP2547341B1/en active Active
-
2013
- 2013-05-22 US US13/899,734 patent/US8969409B2/en active Active
-
2015
- 2015-01-08 JP JP2015002312A patent/JP2015129129A/ja active Pending
-
2016
- 2016-03-16 JP JP2016052406A patent/JP2016153413A/ja not_active Withdrawn
-
2018
- 2018-05-08 JP JP2018089769A patent/JP2018135383A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3108888B1 (en) | 2020-02-12 |
| WO2011115922A1 (en) | 2011-09-22 |
| CA2892104C (en) | 2016-08-30 |
| CA2791081A1 (en) | 2011-09-22 |
| CA2892104A1 (en) | 2011-09-22 |
| KR20130038835A (ko) | 2013-04-18 |
| KR101508047B1 (ko) | 2015-04-06 |
| CN102883722B (zh) | 2014-11-05 |
| JP2018135383A (ja) | 2018-08-30 |
| JP5681276B2 (ja) | 2015-03-04 |
| EP2547341A1 (en) | 2013-01-23 |
| US20110224236A1 (en) | 2011-09-15 |
| JP2013522303A (ja) | 2013-06-13 |
| CA2791081C (en) | 2015-08-25 |
| EP2547341B1 (en) | 2016-09-14 |
| JP2016153413A (ja) | 2016-08-25 |
| ES2611187T3 (es) | 2017-05-05 |
| US20130253049A1 (en) | 2013-09-26 |
| US8609728B2 (en) | 2013-12-17 |
| KR20160132501A (ko) | 2016-11-18 |
| US8969409B2 (en) | 2015-03-03 |
| KR20150027846A (ko) | 2015-03-12 |
| JP2015129129A (ja) | 2015-07-16 |
| CN102883722A (zh) | 2013-01-16 |
| EP3108888A1 (en) | 2016-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2790859T3 (es) | Tratamiento para hipertensión pulmonar | |
| ES2203449T3 (es) | Tratamiento de la hipertension pulmonar por inhalacion de prostaglandinas de bencindeno. | |
| ES2200171T3 (es) | Combinaciones de vasopresina y agentes adrenergeticos para el tratamiento del paro cardiaco. | |
| JP5757677B2 (ja) | 門脈圧亢進症の予防及び／又は治療 | |
| ES2704229T3 (es) | Agonistas selectivos del receptor AT2 para su uso en el tratamiento de la caquexia | |
| ES2906551T3 (es) | Uso de hidrocloruro de landiolol en el tratamiento a largo plazo de taquiarritmias | |
| ES2312588T3 (es) | Regulacion de la secrecion del jugo pancreatico que comprende un agente de regulacion del receptor del lpa. | |
| ES2401671T3 (es) | N,N'-dióxidos de 3,3',4,4'-tetrahidroxi-2,2'-bipiridina para el tratamiento de carcinoma de células renales | |
| JP2020510043A5 (enExample) | ||
| JP2012506434A (ja) | 肺動脈高血圧症の治療方法 | |
| BR112013020377B1 (pt) | Usos de um antagonista do receptor p2y12 reversível na fabricação de um medicamento útil para o tratamento da hipertensão pulmonar | |
| JP2003160509A (ja) | 乳癌の治療 | |
| JP6370801B2 (ja) | 肝疾患または肝障害の治療のための使用および方法 | |
| JP2024023386A (ja) | ウリジンの全身送達のための組成物及びデバイス | |
| ES2261772T3 (es) | Uso de la propionil l-carnitina o de una de sus sales farmacologicamente aceptables para la preparacion de una medicina para el tratamiento de la enfermedad de la peyronie. | |
| US11413273B2 (en) | Prophylactic or therapeutic agent for pulmonary hypertension comprising unsaturated 5-membered heterocycle-containing compound | |
| JP2005060359A (ja) | 血管系病態の治療及び予防のためのジピリダモール、アセチルサリチル酸及びアンギオテンシンｉｉ拮抗薬の使用 | |
| Miyanohara et al. | Scleroderma, The Prone Position and Profound Hypotension: A Case Report | |
| KR20190030805A (ko) | 폐고혈압 예방 또는 치료용 흡입제, 및 이의 투여방법 | |
| ES2564246A1 (es) | Uso de melatonina intravenosa e intracoronaria para limitar el tamaño del infarto agudo de miocardio con elevación del segmento ST | |
| BR112014012261B1 (pt) | Combinação e uso de (s)-4-amino-n-(1-(4-clorofenil)-3- hidroxipropil)-1-(7h-pirrolo [2,3-d] pirimidin-4-il)piperidina-4- carboxamida com um modulador da sinalização do receptor de androgênio |